Kodi S. Ravichandran

Education

  • BVSc, Madras Veterinary College, Madras, India
  • PhD, University of Massachusetts, Amherst, MA
  • Postdoc, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Primary Appointment

  • Professor and Chair, Microbiology, Immunology, and Cancer Biology

Contact

Research Interest(s)

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Research Description

12 generic sildenafil viagra Our laboratory currently focuses on two major areas.

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The overall goal of these studies is to understand the signaling pathways and the consequences of engulfment at the molecular, cellular and whole organism levels. We use a combination of molecular biology, cell biology, biochemistry, coupled with C.elegans and mouse knockout studies, to gain insights on how specific proteins orchestrate the intracellular signaling during engulfment and lead to the immunologically silent clearance of apoptotic cells. These could have implications for future therapies aimed at limiting inflammation (Elliott et al., Journal of Cell Biol, 2010).

2. Intracellular signaling pathways regulating T and B lymphocyte function.

Our particular focus is on how adapter proteins (which do not have any obvious catalytic activity but mediate protein:protein or protein:lipid interactions) regulate B and T cell development and function. We are addressing how the adapter protein Shc regulates specific checkpoints during T cell development in the thymus, as well as B cell development in the bone marrow. We have generated mice carrying targeted shc1 locus that would allow tissue-specific knockout of Shc expression, and also inducible transgenic mice expressing dominant negative forms of Shc. By disrupting Shc function at different stages of development, we are examining the function of Shc during lymphocyte development and subsequent immune responses in the periphery (Ravichandran et al. Science, 1993; Zhang et al. Nature Immunology, 2002; Trampont et al. Molecular Cell Biology, 2006). We have also been focusing on the role of the chemokine receptor CXCR4 (also a coreceptor for HIV-1) in regulating specific developmental steps during thymic T cell development (Trampont et al. Nature Immunology, 2009).

Selected Publications

  • Poon I, Chiu Y, Armstrong A, Kinchen J, Juncadella I, Bayliss D, Ravichandran K. Unexpected link between an antibiotic, pannexin channels and apoptosis. Nature. 2014;507(7492): 329-34. PMID: 24646995 | PMCID: PMC4078991
  • Hochreiter-Hufford A, Lee C, Kinchen J, Sokolowski J, Arandjelovic S, Call J, Klibanov A, Yan Z, Mandell J, Ravichandran K. Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature. 2013;497(7448): 263-7. PMID: 23615608 | PMCID: PMC3773542
  • Juncadella I, Kadl A, Sharma A, Shim Y, Hochreiter-Hufford A, Borish L, Ravichandran K. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature. 2012. PMID: 23235830 | PMCID: PMC3662023
  • Park D, Han C, Elliott M, Kinchen J, Trampont P, Das S, Collins S, Lysiak J, Hoehn K, Ravichandran K. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature. 2011;477(7363): 220-4. PMID: 21857682 | PMCID: PMC3513690
  • Chekeni F, Elliott M, Sandilos J, Walk S, Kinchen J, Lazarowski E, Armstrong A, Penuela S, Laird D, Salvesen G, Isakson B, Bayliss D, Ravichandran K. Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature. 2010;467(7317): 863-7. PMID: 20944749 | PMCID: PMC3006164
  • Elliott M, Zheng S, Park D, Woodson R, Reardon M, Juncadella I, Kinchen J, Zhang J, Lysiak J, Ravichandran K. Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo. Nature. 2010;467(7313): 333-7. PMID: 20844538 | PMCID: PMC3773546
  • Kinchen J, Ravichandran K. Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells. Nature. 2010;464(7289): 778-82. PMID: 20305638 | PMCID: PMC2901565
  • Elliott M, Chekeni F, Trampont P, Lazarowski E, Kadl A, Walk S, Park D, Woodson R, Ostankovich M, Sharma P, Lysiak J, Harden T, Leitinger N, Ravichandran K. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009;461(7261): 282-6. PMID: 19741708 | PMCID: PMC2851546
  • Trampont P, Tosello-Trampont A, Shen Y, Duley A, Sutherland A, Bender T, Littman D, Ravichandran K. CXCR4 acts as a costimulator during thymic beta-selection. Nature immunology. 2009;11(2): 162-70. PMID: 20010845 | PMCID: PMC2808461
  • Kinchen J, Doukoumetzidis K, Almendinger J, Stergiou L, Tosello-Trampont A, Sifri C, Hengartner M, Ravichandran K. A pathway for phagosome maturation during engulfment of apoptotic cells. Nature cell biology. 2008;10(5): 556-66. PMID: 18425118 | PMCID: PMC2851549
  • Park D, Tosello-Trampont A, Elliott M, Lu M, Haney L, Ma Z, Klibanov A, Mandell J, Ravichandran K. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature. 2007;450(7168): 430-4. PMID: 17960134
  • Stites E, Trampont P, Ma Z, Ravichandran K. Network analysis of oncogenic Ras activation in cancer. Science (New York, N.Y.). 2007;318(5849): 463-7. PMID: 17947584
  • Lu M, Kinchen J, Rossman K, Grimsley C, deBakker C, Brugnera E, Tosello-Trampont A, Haney L, Klingele D, Sondek J, Hengartner M, Ravichandran K. PH domain of ELMO functions in trans to regulate Rac activation via Dock180. Nature structural & molecular biology. 2004;11(8): 756-62. PMID: 15247908
  • Brugnera E, Haney L, Grimsley C, Lu M, Walk S, Tosello-Trampont A, Macara I, Madhani H, Fink G, Ravichandran K. Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nature cell biology. 2002;4(8): 574-82. PMID: 12134158
  • Zhang L, Camerini V, Bender T, Ravichandran K. A nonredundant role for the adapter protein Shc in thymic T cell development. Nature immunology. 2002;3(8): 749-55. PMID: 12101399
  • Gumienny T, Brugnera E, Tosello-Trampont A, Kinchen J, Haney L, Nishiwaki K, Walk S, Nemergut M, Macara I, Francis R, Schedl T, Qin Y, Van Aelst L, Hengartner M, Ravichandran K. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell. 2001;107(1): 27-41. PMID: 11595183